Marijuana is the most commonly used illegal drug in the United States. Over 65
million Americans (31% of the US population aged 12 and older) are estimated to
have used marijuana: 1 its mean retail sales value in the United States is
approximately $10 billion.2 Despite its long-standing popularity and
increasing use among youth in recent years,1,3 we still know little about
long-term health risk associated with marijuana use. Harvard policy analyst
Mark Kleiman recently concluded that "aside from the almost self-evident
proposition that smoking anything is probably bad for the lungs, the quarter
century since large numbers of Americans began to use marijuana has produced
remarkably little laboratory or epidemiological evidence of serious health
damage done by the drug."4(p.253) Similar appraisals of the health effects of
cannabis were offered in the two most comprehensive reviews from the 1980s.5,6

More currently, Hall and co-authors concluded that while there are no
well-established health or psychological effects of chronic cannabis use, the
following were considered to be probable major adverse effects: respiratory
diseases associated with smoking as the method of administration, including
chronic bronchitis and pre malignant histopathological changes in the lung;
development of a cannabis dependence syndrome; and subtle forms of cognitive
impairment.7(p. 16)

The only other large-scale study of marijuana use and mortality was performed
in a cohort of 45,540 male Swedish conscripts, aged 18 through 20 years at
baseline and followed for 15 years.8 In this study, the relative risk (RR) for
mortality associated with marijuana use (more than 50 times) was 1.2 (95%
confidence interval[C]=0.8, 1.9) after adjustment for social background.

We report here the findings of a study of the relationship of marijuana use to
mortality in a cohort of over 65.000 members of a large prepaid health plan.
Data on marijuana use in this cohort were collected before the "war on drugs"
escalated in the latter half of the 1980s, which may have resulted in under
reporting of illegal drug use.9 Mortality is one of several health outcomes
being studied; other endpoints include cancer incidence and outpatient
utilization for respiratory illnesses and injuries. We have hypothesized that
marijuana use would be associated with increased risk of respiratory disease
and injury.

The main overall findings were an increased risk of total mortality associated
with marijuana use in men but not in women. The increased risk of total
mortality in men was explained by the strong relationship between marijuana use
and AIDS mortality. Marijuana use was unassociated with non-AIDS mortality in
men.

The question of the effect of marijuana use on AIDS mortality is an important
one. Marijuana use has been advocated as a therapeutic adjunct to ameliorate
the nausea and loss of appetite commonly associated with the wasting syndrome
in AIDS.17 We have provided substantial evidence that the increased risk of
AIDS mortality in the total study cohort probably resulted from uncontrolled
confounding by homosexual behavior. Other studies have reported a
substantially higher prevalence of marijuana use in homosexual and bisexual
men, supporting the hypothesis that marijuana use is a marker for homosexuality
or bisexuality.18-20

There are several other potential explanations for the increased risk of AIDS
in marijuana users. Marijuana smoking might theoretically place AIDS patients
at increased risk of infection because of its irritative effects on the
respiratory system or because of infectious contaminants (e.g., fungi) in
marijuana. Other potential explanations include marijuana use as a result of
having HIV and AIDS, rather than preceding the disease; and possible
immunosuppressive properties of marijuana.

The use of alcohol and nonmedical psychoactive drugs, including marijuana, is
associated with risky sexual behavior such as unprotected intercouse,20 but
methodological limitations have made it impossible to determine causality.21
Marijuana use may serve to a certain extent as a marker of intravenous drug
use. However, the relative risk of AIDS mortality associated with marijuana
use did not diminish when the analysis was limited to men who were nonsmokers
of tobacco and occasional alcohol drinkers, a subgroup unlikely to contain many
parental drug users. Additional evidence against marijuana as a marker for
parental drug use was the finding of only one case of infective endocarditis in
Kaiser Permanente hospitalization record of the AIDS decedents.

The lack of increased mortality during the first 5 years of follow-up suggests
that therapeutic use of marijuana at baseline for AIDS-related symptoms has
little, if any, explanatory effect on the association between marijuana use and
AIDS. Furthermore, the majority of AIDS patients initiated marijuana use long
before the onset of clinical disease; nearly two thirds (65%) of AIDS patients
reported initiation before 1976, when HIV infection in the San Francisco Bay
area was either nonexistent or negligible.22

While marijuana and its psychoactive cannabanoids possess known
immunosuppressive qualities, there is no consensus as to whether typical doses
result in clinical immunosuppression in humans.23 Marijuana use has been
associated with a higher prevalence of seropositivity for HIV in some
cross-sectional studies of homosexual and bisexual men,20.24 but it has not
been shown to be an independent predictor of seroconversion,25 not does it
increase the risk of AIDS in seropositive men.24

The nearly significant increase in mortality risk from injury or poisoning for
female current marijuana users was consistent with our hypothesis that
marijuana use is a risk factor for death due to injury. Marijuana is known to
decrease psychomotor performance; some studies have implicated its use in motor
vehicle crashes.7(pp43-50) Marijuana use is also strongly associated with
alcohol use, another major risk for accidental death. There were too few
deaths to meaningfully study the other main hypothesis, that marijuana use
would be associated with increased respiratory disease mortality. Another
study performed on a subgroup of this cohort showed that daily or near-daily
marijuana users who were not tobacco cigarette smokers had a 19% higher risk of
outpatient visits for respiratory disorders than non users of both
substances.26

The major limitations of this study include its reliance on self-report for
ascertainment of marijuana use status; the inability to study changes in
marijuana use status during follow-up; a lack of lengthy follow-up into the
geriatric age range (maximum follow-up, 12.5 years; maximum age reached, 63
years); a lack of information regarding other illegal drug use; and potential
underascertainment of mortality (noted earlier). Estimates of marijuana use
were similar to those obtained during this period by the National Household
Survey on Drug Abuse, the most authoritative source of illegal drug use
information for US adults.27 The lack of longitudinal data regarding use
status is common to many cohort studies. It seems unlikely that "ever"
marijuana use status would have changed substantially over time, because
relatively few adults in this cohort are likely to have initiated marijuana use
during follow-up in a period (1980s) when there was a marked secular decline in
self-reported marijuana use in the United States.1 It is possible that
relationships between marijuana use and mortality might be found with
longer-term follow-up or later in life. It is likely that if information on
subjects' use of other illegal drugs had been available, adjustment for other
drug use would have lowered the relative risk estimates for marijuana use.

As noted earlier, relatively few adverse clinical health effects from the
chronic use of marijuana have been documented in humans.7(p16) The
criminalization of marijuana use may itself be a health hazard, since it may
expose the consumer to violence and criminal activity.28 While reducing the
prevalence of drug abuse is a laudable goal, we must recognize that marijuana
use is widespread despite the long-term, multibillion dollar War on Drugs.
Therefore, medical guidelines regarding its prudent use should be established
skin to the commonsense guidelines that apply to alcohol use. Unfortunately,
clinical research on potential therapeutic uses for marijuana has been
difficult to accomplish in the United States, despite reasonable evidence for
the efficacy of tetrahydrocannabinol (THC) and marijuana as anti emetic and
anti glaucoma agents and the suggestive evidence for their efficacy in the
treatment of other medical conditions, including AIDS.7(pp185-262)

In summary, this study showed little, if any effect of marijuana use on
non-AIDS mortality in men and on total mortality in women. The increased risk
of AIDS mortality in male marijuana users probably did not reflect a causal
relationship, but most likely represented uncontrolled confounding by male
homosexual behavior. The risk of mortality associated with marijuana use was
lower than that associated with tobacco cigarette smoking.

19. Skinner WF, Otis MD. "Drug Use among Lesbian and Gay People: Design,
Insights, and Policy Issues from the Trilogy Project. In: Proceedings of the
Research Symposium on Alcohol and Other Drug Problem Prevention among Lesbians
and Gay Men. Sacramento, Calif.: California Dept of Alcohol and Drug
Programs; October 1992: 34-60.